Transendothelial migration of lymphocytes in chronic lymphocytic leukaemiais impaired and involves down-regulation of both L-selectin and CD23

Chronic lymphocytic leukaemia (B-CLL) is characterized by a progressive acc umulation of B lymphocytes in blood and bone marrow and high concentrations of soluble CD23 and L-selectin are found in the serum of these patients. I n this study lymphocytes from normal subjects and patients with B-CLL were allowed to undergo transendothelial migration across confluent layers of hu man umbilical vein endothelial cells, Lymphocytes in B-CLL samples showed a n impaired capacity to migrate while the minor proportion of normal T cells was enriched by a mean of 2.5-fold in the transmigrated lymphocytes. In co ntrast, the ratio of B to T lymphocytes in normal preparations was unchange d in the transmigrated population, The expression of adhesion molecules on B-CLL lymphocytes before and after transendothelial migration was studied b y now cytometry which showed that 71 +/- 5% of L-selectin was lost from the surface of transmigrated lymphocytes. T and B cells from normal subjects a lso showed a major loss of L-selectin after transmigration. B-CLL lymphocyt es and normal B cells expressed CD23 but this molecule was down-regulated f ollowing transendothelial migration, whereas the expression of VLA-4, ICAM- 1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with oxidized ATP, a n irreversible inhibitor of P2Z/P2X7 purinoceptors, retained their capacity for transendothelial migration and showed the same loss of L-selectin as c ontrol leukaemic lymphocytes. Our results show that B-CLL lymphocytes have impaired ability for transendothelial migration compared to normal peripher al blood lymphocytes. Moreover, transendothelial migration involves a unive rsal loss of 1-selectin and CD23 from lymphocytes which suggests that the h igh serum levels of soluble L-selectin and CD23 observed in B-CLL may be ge nerated by shedding during the process of transendothelial migration.